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Increased maternal age is known to increase the risk of congenital heart disease in offspring; here, this link is investigated by transplanting ovaries between young and old mice, revealing that the maternal-age-associated risk is independent of the age of the ovaries but depends on the age of the mother, and that this risk can be mitigated by maternal genetic background or exercise.

Sharks and rays are vital coral reef species. This study shows that nearly two thirds (59%) of the 134 coral-reef associated species are threatened with extinction. The main cause of their decline is found to be overfishing, both targeted and unintentional, and extinction risk is greater for larger species found in nations with higher fishing pressure and weaker governance.

Karol Cichewicz and Jay Hirsh developed a free, open-source, cloud-based application called ShinyR-DAM for analyzing Drosophila activity, sleep and circadian rhythms. ShinyR-DAM allows users to analyze their data quickly in customizable ways, improving the productivity of researchers.

Analysis of rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

In this Review, Rajagopalan and colleagues summarize the sources of greenhouse gas emissions related to the provision of cardiovascular health care and suggest strategies to reduce carbon emissions and costs, including the use of renewable energy, waste reduction and disease prevention.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

A mouse study reveals that acetylcholine signalling networks have a role in the regulation of body weight homeostasis, with increased activity of cholinergic neurons decreasing food consumption through downstream hypothalamic targets.

All forms of diabetes eventually lead to a reduction in insulin-secreting pancreatic β-cells. Here, the authors report aminopyrazine derivatives, which induce proliferation of rodent as well as human β-cells and improve glucose metabolism in a mouse model of type 1 diabetes.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Polymorphisms in a primate-specific isoform of K⁺ channel KCNH2 are associated with schizophrenia. This isoform induces a rapidly deactivating K⁺ current and high-frequency neuronal firing pattern. The disease-associated alleles predict lower intelligence quotient scores, lower speed of cognitive processing and altered memory. This channel isoform represents a potential new drug target for psychotherapypages 488–490.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

Bevacizumab with standard chemotherapy improved overall survival in colorectal and lung cancer patients and progression-free survival in breast cancer patients, but this combination failed to increase survival in patients with previously treated and refractory metastatic breast cancer. Reasons for these contrasting results, the mechanisms behind normalization of tumor vasculature for improved drug and oxygen delivery, and the need for biomarkers and imaging techniques to guide patient selection and protocol design are discussed.

Most brain tumors secrete high levels of vascular endothelial growth factor, which can lead to an abnormally permeable tumor vasculature. This hyperpermeability causes vasogenic cerebral edema and increased interstitial fluid pressure, which can prevent adequate penetration of chemotherapy agents to the tumor. This Review focuses on the pathophysiology of vasogenic edema and the potential utility of agents that target angiogenesis, and particularly the vascular endothelial growth factor pathway.

No validated biomarkers currently exist for appropriately selecting cancer patients for antiangiogenic therapy. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged as suitable candidate biomarkers, but all require prospective validation. The authors discuss the current challenges in establishing biomarkers, the advantages and disadvantages of systemic, circulating, tissue and imaging biomarkers, and the future opportunities for validating biomarkers of antiangiogenic therapy.

Tumours rely on blood vessels for survival and growth. Jain and colleagues review the mechanisms by which malignant brain tumours stimulate the formation of new blood vessels, and discuss the latest methods for monitoring and treating brain tumours with anti-VEGF agents.

Radiotherapy is one of the most important and effective therapies used to treat cancer. Particle therapy is an emerging technique and there is debate surrounding its cost-effectiveness. The authors of this Review present clinical results in the field and discuss the research questions that have arisen with this technique.

Brain metastases remain a serious obstacle in the successful treatment of patients with solid tumors. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients.

Charged particle therapy (CPT) offers advantages over conventional radiotherapy, such as higher local control of the tumour and the potential for less damage to healthy tissues. Despite the advantages of CPT, only a small number of controlled randomized clinical trials have compared it to conventional radiotherapy. The latest clinical data on the use of CPT, dose calculations and delivery, cost-effectiveness issues, current status, and future directions are discussed.

Conventional radiotherapy with X-rays is being replaced by radiotherapy with high-energy charged particles, an approach that better spares healthy tissue from radiation but is associated with higher costs. Evidence supporting the cost-effectiveness of either modality can only come from the results of randomized clinical trials. The authors of this Review discuss ongoing randomized trials of charged-particle therapies as well as aspects related to radiobiology, which need to be taken into account in order to fully exploit the therapeutic potential of charged particles.

Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases.